In recent years, liquid chromatography, including in this term a wide variety of experimental and analytical techniques, has become bY far the preferred technique for laboratory analysis of the properties of polymers. Stated generally, the principles of liquid chromatography involve the supplying of a liquid sample (for example, of polymer in solution) to a separation column containing a separation medium at very high pressure. Over time, a sample stream elutes from the column, the constituents of which vary during elution as a function of the properties of the material being analyzed and of the separation medium. As mentioned, a wide variety of different liquid chromatographic techniques are known and will not further be discussed here.
As mentioned, substantially all liquid chromatographic techniques involve the supply of a sample fluid to a separation column at high pressure, typically on the order of 500 to 5000 psig. Accordingly, a high pressure pump is required. As a rule, the pumps used in liquid chromatography are mechanically-driven piston pumps of one type or another, all of which have certain unavoidable defects. More particularly, all piston pumps require a seal between a piston or the equivalent and a cylinder or the equivalent. These seals are subject to wear over time and accordingly maintenance must be performed from time to time. Another significant defect of piston pumps is that they are extremely expensive. One pump which may be considered generally representative of the state of the art at the time of filing of this application costs a minimum of $4,000 and even then requires modification in many circumstances. Variation of the flow rate of prior art piston pumps typically requires adjustment of a mechanical linkage, which also is subject to wear over time; therefore, such pumps require periodic calibration if flow rates are to be kept more or less constant.
Many if not most liquid chromatographic techniques are desirably implemented by supplying sample to the column in increments of constant volume, that is, at a constant flow rate. The provision of equal-volume samples to the separation column is difficult with ordinary piston pumps, because the volume of sample pumped for a given piston stroke can vary with varying conditions in the pump (for example, temperature and seal wear) and in the column (for example, clogging) over time. It would be desirable to provide volume-related automatic feedback control signals to the pump from an accurate flowmeter disposed downstream of the pump, so as to be able to provide substantially constant flow, that is constant increments of volume per unit time. As mentioned above, however, adjustment of the flow rate provided by mechanical pumps frequently involves adjustment of a mechanical linkage, which can be difficult to perform automatically, such that control based on feedback of a flow rate signal is sometimes awkward to implement. Furthermore, mechanical linkages of some types only provide flow rate adjustment in finite increments, so that the exact flow rate desired may not be available. Therefore, a high pressure pump suited to automatic flow rate control by means of feedback and being operable to provide substantially any desired flow rate is needed by the art.
Another deficiency of conventional piston pumps as used in liquid chromatography is that their output inherently includes pressure pulses, which appear as noise in the output signal provided by the liquid chromatographic apparatus. A wide variety of pressure damping techniques and devices are known, none of which are entirely satisfactory and all of which necessarily involve some additional complication. It would therefore be desirable to provide a pump which at least offers the possibility of improved continuity of flow.
These problems are generally recognized in the art. See, for example, Abrahams et al. U.S. Pat. No. 3,855,129 which purports to address and solve some of the problems existing with prior art piston pumps. The Abrahams et al device is, however, an improved piston pump, and would appear likely to suffer from many of the deficiencies noted.
In addition to piston pumps, the prior art also teaches what may be termed "thermal pumps." Speaking generally a thermal pump comprises a fluid chamber in series with first and second check valves on its inlet and outlet sides. Heat is supplied to the chamber, causing the fluid in it to expand, possibly undergoing a partial change of phase, and forcing a portion of the fluid past the outlet check valve. Upon cessation of application of heat, the fluid in the chamber contracts, causing additional fluid to be drawn past the inlet check valve. The process is then repeated.
Proctor U.S. Pat. No. 1,973,541 shows a thermal pump for use in a deep oil well, in which these general principles are employed. See also Hutton U.S. Pat. No. 1,630,943 also generally showing a pump of this type, and disclosing that it may be useful in connection with "certain fluid testing devices and the like". However, both the Proctor and the Hutton pumps have significant defects which would render them useless in the modern liquid chromatographic environment. For example, neither seems suitable for generating the very high pressures required. Nor does either appear to show any means by which a relatively sophisticated feedback control could be incorporated in order to provide a relatively continuous flow rate. Hutton in particular shows a relatively crude thermostatic control arrangement which would seem quite unsuited to a laboratory environment.
See also Brown U.S. Pat. No. 3,819,299, which shows a "magnetocaloric pump" in which a fluid is caused to expand by being heated. The heating is accomplished by applying a magnetic field to a magnetocaloric material, that is, one which is heated when subjected to a magnetic field, the material being in thermal contact with the fluid to be pumped. Brown provides only timers for control.
Bowen et al. U.S. Pat. No. 3,195,806 shows a pump for high pressure pumping of gases. Bowen et al. teach a pump comprising a lengthy capillary of electrically resistive material disposed between first and second check valves. A current is passed through the capillary, heating its contents and causing them to expand, thus being pumped through the outlet check valve. Bowen et al. do not teach a control system other than a power switch.
A further document showing pumping of liquid by heating thereof in a chamber disposed between inlet and outlet check valves is Van Hise U.S. Pat. No. 1,686,887. Van Hise also shows a power switch as the only control element.
Mandroian U.S. Pat. No. 4,265,600 describes a diaphragm-type thermal pump, in which the fluid to be pumped is separated by a flexible diaphragm from a pumping fluid. The pumping fluid is heated by passing an electric current through a resistive filament disposed in a chamber containing the pumping fluid. The pumping fluid is a volatile liquid or gas, such that when heated it expands, forcing the diaphragm into a second chamber filled with the fluid to be pumped. The second chamber is connected by check valves to a source and sink of fluid, e.g. a container of saline solution, and a patient, respectively.
Mandroian teaches feedback of flow rate and/or pressure signals for control of supply of current to the heating element, and teaches that use of the diaphragm arrangement simplifies preservation of the sterility of the pumped fluid. The Mandroian pump does not appear suitable for liquid chromatographic applications, as it is apparently limited to very low pressures. Note the embodiment of FIG. 3, which the pumping fluid chamber is vented to the atmosphere. Further it would appear that Mandroian is limited to pulsatile flow; see col. 4, lines 38-54. As mentioned above this is frequently undesirable.
Accordingly, a need exists in the art for an improved pump suitable for use in liquid chromatographic and other high-pressure, low flow rate applications.